Summary As prescription opioid use and heroin use has reached epidemic proportions, there has been a corresponding increase in infants born with neonatal abstinence syndrome (NAS). NAS is a postnatal withdrawal syndrome usually caused by in utero opioid exposure, and one infant is born every 25 minutes in the United States with signs of drug withdrawal. Nationally, NAS rates increased nearly five-fold from 2000 to 2012, and substantial state-to-state and rural/urban variation exists. States have enacted a variety of policy responses to address the dramatic rise in NAS rates, some of which directly target NAS or women of childbearing age, while others are designed to decrease the overall number of individuals using opioids or suffering from opioid use disorder. There has been a paucity of empirical studies examining to what extent different state policy approaches are associated with variation in NAS rates at the sub-state level and within key subgroups (e.g., rural residents, Medicaid-enrollees). Furthermore, it is not known whether policies differentially influence NAS rates among socioeconomically disadvantaged individuals, populations who historically have been disproportionately impacted by drug laws, populations with less access to healthcare, and different populations of women who use opioids in pregnancy (e.g., who are prescribed opioid analgesics, receive medication-assisted treatment, and/or have an opioid use disorder). In this proposal, we will use two complementary data sources to 1) estimate NAS rates for key subgroups over time to determine variation in rates at the sub-state level using data from multiple states; and 2) characterize the association between variation in NAS rates and state-level policies likely to influence NAS overall and among historically disadvantaged populations. This exploratory analysis will lay the groundwork for a subsequent R01 study that will assess the impact of state policies on NAS rates overall and among key subgroups. The goal of this preliminary study and the planned subsequent R01 proposal is to facilitate more informed policymaking to prevent adverse outcomes for women and infants impacted by the opioid epidemic.